Protecting materials against fungi by applying substituted dithiono and thiono-oxo-thiadiazolidines



Patented Dec. 9, 1958 2,863,803 may be readily prepared by contacting the corresponding PROTECTING MATERIALS AGAINST FUNGI BY APPLYING SUBSTITUTED DITHIONO AND THIONO-OXO-THIADIAZOLIDIL IES Isaac Benghiat, Bronx, N. Y., James B. Bowers, Mountain View, Calif., and George E. Lukes, Irvington, and Silvio L. Giolito, Whitestone, N. Y., assignors to Stanffer Chemical Company, a corporation of Delaware No Drawing. Application May 13, 1957 Serial No. 658,492

6 Claims. (Cl. 167-33) wherein R is an alkyl or phenyl group, R is also an alkyl or phenyl group and X is an O or S atom. Certain of these compounds may be prepared by oxidizing sodium N-alkyl dithiocarbamates, RNHCS NA.

More particularly, this invention relates to chemical compositions which have fungicidal and fungistatic properties, these chemical compositions being represented by the general formula set forth above wherein R and R are preferably methyl, ethyl, propyl, butyl, pentyl and hexyl. The letter X designates oxygen or sulphur. The preferred compounds of this invention are 2,4-dimethyl- 3,5- dithiono-1,2,4 thiadiazolidine (N-l045); 2,4-dimethyl-3,thiono-S-oxo-1,2,4-thiadiazo1idine (N-l038 di ethyl analogs of the above two compounds (N-1426 and N-1425); the dipropyl analogs of the above (N-1483 and N-1490); the dibutyl analog of N-1045 (N-1427); and the hydrobromide of the dihexyl analog of N-1045 (bl-444,8). The phenyl analogs of 1045 and 1038 have also been tested and found effective, but to a lesser extent than certain of the other compounds tested above. Also, compounds having differing substitutents as R and R are effective as fungicides, but because of the greater ease of manufacture of the compounds having identical substitutents in the R and R position, the latter are preferred. Since the names of these compounds are somewhat unwieldy, code numbers have been assigned (those shown in parentheses above) and throughout the balance of the specification reference is made to these compounds by said code numbers. A tabulation of the codes and structures involved is as follows:

dbl-LE8 was used as the hydrobromide.

some of these compounds, the dialkyl thiadiazolidines,

moist, solid sodium N-alkyl dithiocarbamate with air, or an oxygen-containing gas, at elevated temperatures. The formation of the dialkyl thiadiazolidines under these conditions is favored if the solid dithiocarbamate is in the form of a moist (hydrated) fine powder. In the case of N-1045, it has been found that it may be prepared by contacting moist, hydrated solid sodium N-methyl dithiocarbamate with air in a pneumatic-conveying drier (flash drier) as described, hereinafter, more fully in the non-limiting Example II. Other means, well-known in the art, of contacting the moist, solid dithiocarbamates with an oxygen-containing gas at elevated temperaturesv are suitable for this preparation. Temperatures should be above 100 C., and preferably in the range of about 130 to 250 C.

In order to show the effectiveness of these compounds as fungicides, the following tests were carried out:

Agar plate test.In testing the compound for fungitoxicity by this method, the compound is dispersed evenly throughout 20 ml. of warm potato dextrose agar on a petri dish. A series of plates containing various concentrations of the compound are prepared for each fungus species used. When the agar has cooled and solidified, the center of each plate is seeded with a few spores of the desired fungus. After seven days incubation in the dark under controlled temperatures of 20 C., the diameter of the fungus colony on each plate is measured and the relationship between the growth on each plate and that on an untreated but seeded control plate is recorded as percent control (or percent inhibition of growth). The results with N-1045 are set forth below in tabular form:

TABLE I Percent control at p.p.m, p.p.m, p.p.m. .p.m. 500 100 50 p 25 Aspergillus niger 100 100 10 Scleratz'nia fructicola 100 100 100 Stemphylium sp 100 100 .100 100 Vial test.-Additional tests were conducted using a variety of the fungicidal materials of this invention, a test termed the vial test being substituted for the agar plate test. The method is generally the same except that lidequipped bottles of 1 02. capacity were employed in place of theagar plates, thus allowing for the sealing in of the contents and careful control of the concentration of the fungicide in the presence of the fungus under treatment. Volatilization losses are prevented.

In testing compounds for fungitoxicity by this method, the compound is dispersed evenly through 10 ml. of liquid malt solution in the bottles. A series of bottles are prepared containing various concentrations of the compound for each fungus species. After treatment, each bottle is seeded with a few spores of the desired fungus.

After seven days incubation in the dark at a temperature" TABLE II Percent inhibition at concentrations in p. p. m.

Aspergilltls nigcr Scirrotinia [ructz'cola Stemphylium 5]). Compound (0) 100 100 100 100 H 100 100 llll) 1th) ll ll l U llll) N10 100 (O) Q l) 100 100 100 100 It 100 100 100 100 (D) l) 0 (l i. U 0 0 20 2O 20 20 20 M N-l490. 100 100 NHSZ 20 20 N-1043 84 N10C G.. 36

The parentheses designate instances wherein the fungus, while not destroyed, Was inhibited.

LD-95 and LD-SO points, i. e., the concentration of the n toxic substance necessary to prevent germination of 95% and 50%, respectively, of the test organism.

In these tests it was found that with S. jrnclicola, compound N-l045 had an LD-SO of approximately 10 p. p. m. This compared very favorably with other foliage fungicides such as zinc ethylene bis dithiocarbamate which had an LD-SO of 24 p. p. m. in the same test.

Foliage test.-Thcreafter a series of foliage tests were run wherein pinto bean plants, sprouted and grown seven days in a bottom-heated sand bed in a greenhouse, were potted two plants per three inch pot. Three days after transplanting, the terminal growth was pinched from each plant, leaving the two primary leaves. The chemicals to be tested were then sprayed on both the upper and lower surfaces of the primary leaves as aqueous dispersions. A small quantity of wetting agent was included in the dispersant (distilled water), and care was taken to assure small particle size of the test compound.

After the deposit dried, duplicate pots of plants from each concentration were inoculated with the test fungi, Uromyces phaseoli (bean rust) and Eryrip/ze polygoni (bean powdery mildew). The plants inoculated with mildew were placed directly in the greenhouse, while the rust-inoculated plants were incubated in a high humidity chamber for 18 hours before removal to the greenhouse. Readings of the control were taken ten days following spraying and inoculation and the results are expressed below as percent control as compared with untreated checks.

A series of additional tests were run on N-IO S, the results of which are set forth below. These tests involved foliage screening wherein the host plants were sprayed with the fungicide which was then allowed to dry. Thereafter the plants were inoculated with a spore suspension of the selected fungus. Plants were held in the greenhouse under suitable conditions until the disease developed on unsprayed checked plants.

TABLE IV Percent control atp. p. m., p. p. 111., p. p. m., 1,000 500 Rust f Bean n Beans 100 100 100 Powdery Mildew on Bonus. 99 7'5 25 Grey Blight on lomato- 100 75 50 Early Blight on Tomato n 100 100 50 Additional fungi involved in these tests were:

Grey blight-Stenzphylium solani Early blight-Altcrnaria solani As set forth earlier, these compounds may be prepared in several fashions, one of which is the two-step oxidation of sodium N-alkyl dithiocarbamate dihydrate. This procedure may be carried out in accordance with the following:

Whereas the literature recommends the use of alcoholic ammonia for the isomerization, it has been found that this proceeds very readily simply on recrystallizing the initial isomer from hot isopropyl alcohol; i. e., five minutes in boiling isopropyl alcohol is sufiicient to effect the isomerization.

It has also been found that a far easier method exists which is entirely unknown to the art, the simple passing of a slurry of sodium N-alkyl dithiocarbamate through a flash drying apparatus. It has been found that this conversion of the dithiocarbamate to the dialkyl thiadiazolidine is favored if the solid carbamate is in the form of a moist, very fine powder.

Examples of the use of these two methods for the preparation for the compounds of this invention are set forth below. These examples are 'by way of illustration and are not to be taken as imposing limitations on the scope of the invention other than as are set forth in the appended claims.

EXAMPLE I In the laboratory preparation of N-1045, 330 g. (2.0 moles) of sodium N-methyl dithiocarbamate dihydrate (solid) were slurried with 500 cc. of ethanol, 256 g. (1.0 mole) of iodine were added with stirring in small increments. The reaction temperature was maintained at 20 C. by cooling in an ice bath. The reaction was practically instantaneous. After all of the iodine had been added, the reaction mixture was poured into 2 liters of water and filtered.

Yieldcrude dimethyl thiuram disulfide, 210 g., 99 percent; M. P. 93 C.

Crystallization from methanol gave the pure dimethyl thiuram disulfide.

21 g. (0.1 mole) of freshly prepared dimethyl thiuram disulfide were slurried in 100 cc. of chloroform and chilled to 10 C. in an ice bath. 16 g. (0.1 mole) of Br in 50 cc. of chloroform were added slowly maintaining the reaction temperature at 1015 C. A reddishbrown ppt. was obtained. It was filtered oif, washed with chloroform and then slurried with cold sodium bicarbonate solution. There was little reaction. The material was filtered off and slurried with ethanol and 28 percent ammonium hydroxide was added drop by drop until the mixture was alkaline. The ppt. was now filtered off. The product, the isomer of the desired material, was crystallized from cold chloroform by addition of ligroin. First crystallization, M. P. 72-76"; 2nd, 80-82", 3rd, 84"; 4th (from benzene and ligroin),

.84". Yield, 6 g. or 33 percent of 3 g. of this isomer, M. P. 84 C., was boiled 5 minutes in isopropyl alcohol. The solution was chilled and allowed to crystallize. 2 g. of N-1045, M. P. 122-123 C., were obtained. The product has the formula:

S =0 --N 0 Ha ClH l l EXAMPLE II A solution of sodium N-methyl dithiocarbamate was concentrated by heating to approximately 70 C. and by placing the system under vacuum for several hours. Upon cooling the aqueous solution, a thick slurry of crystalline material was obtained. The product was centrifuged to remove the aqueous phase and the wet solid material was conveyed in air through a pneumatic conveying drier (flash drier) at approximately 150170 C. The product was then recycled through the flash drier at approximately 150 C.170 C. The product warmed spontaneously on standing overnight and developed a strong isothiocyanate odor. The product was slurried in water, filtered, and the water-insoluble fraction was recrystallized from isopropyl alcohol as in Example I, to obtain N-1045, M. P. 122125 C. The filtrate containing the water-soluble fraction, which was mainly sodium N-methyl dithiocarbamate, was further concentrated under vacuum. The crystallization, centrifugation, and flash drying steps were repeated to yield additional water-insoluble N-1045.

Fungicides of the present invention may be applied by methods well known to those skilled in the art. They may be used in solutions of organic solvents, such as acetone, dispersed in water, made into aerosols or mixed with a dry powder carrier for application to plants, animals :or soil. They may be vaporized in confined spaces for their fumigation effect for protecting grain and the like. Solutions or emulsions may be used for spraying or dipping articles such as leather or cloth. A wide range of concentrations may be used, since the solutions of the compounds of the present invention are effective for some purposes, even in concentrations of less than one part per million.

In the claims hereinafter, reference is made to material which is protected from attack by fungus. It is to be understood that the term material includes plants, animals and inanimate objects which are subject to fungus attack.

Obviously many modifications and variations of the invention as hereinbefore set forth may be made without departing from the spirit and scope thereof, and therefore only such limitations should be imposed as are indicated in the appended claims.

We claim:

1. A method of protecting material from attack by fungus comprising applying thereto a small amount of the compound having the formula:

wherein R is a member of the class consisting of phenyl and alkyl groups, wherein R is a member of the class consisting of phenyl and alkyl groups, and'wherein X is a member of the class consisting of S and O.

2. A method of protecting material from fungus attack comprising applying thereto a small amount of 2,4- dimethyl-3,5-dithiono-1,4-thiadiazolidine.

3. A method of protecting material from fungus attack comprising applying thereto a small amount of 2,4- dimethyl-3-thiono5-oxo-1,2,4-thiadiazolidine.

4. A method of protecting material from fungus attack comprising applying thereto a small amount of 2,4-

diethyl-3,5-dithiono-1,2,4-thiadiazolidine.

5. A method of protecting material from fungus attack comprising applying thereto a small amount of 2,4-diethyl-3 -thiono-5-oxo-1 ,2,4-thiadiazolidine.

6. A method of protecting material from fungus attack comprising applying thereto a small amount of 2,4-din-propyl-3-thiono-5-oxo-1,2,4-thiadiazolidine.

References Cited in the file of this patent UNITED STATES PATENTS 2,148,909 Maier Feb. 28, 1939 2,255,903 Shonle et a1. Sept. 16, 1941 2,285,410 Bousquet et a1. June 9, 1942 2,510,725 Sundholm et al June 6, 1950 OTHER REFERENCES Chem. Abst. (1), vol. 49, p. 45441, (1955). Chem. Abst. (2), vol. 44, p. 1101b, (1950). Bambas: The Chemistry of Heterocyclic Compounds, pp. 72-74, 1952. 

1. A METHOD OF PROTECTING MATERIAL FROM ATTACK BY FUNGUS COMPRISING APPLYING THERETO A SMALL AMOUNT OF THE COMPOUND HAVING THE FORMULA:
 2. A METHOD OF PROTECTING MATERIAL FROM FUNGUS ATTACK COMPRISING APPLYING THERETO A SMALL AMOUNT OF 2,4DIMETHYL-3,5-DITHIONO-1,4-DITHADIAZOLIKINE.
 3. A METHOD OF PROTECTING MATERIAL FROM FUNGUS ATTACK COMPRISING APPLYING THERETO A SMALL AMOUNT OF 2,4DIMETHYL-3-THIONO-5-OXO-1,2,4-THIADIAZOLIDINE. 